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CANCER VACCINES SET TO UNLOCK ‘NEW TREATMENT PARADIGM’ WITH MERCK/MODERNA DATA


Merck and Moderna have been collaborating since 2016. PHOTOS: REUTERS
Updated
Jun 9, 2023, 7:48 PM SGT
Published
Jun 5, 2023, 8:45 PM SGT
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https://str.sg/i3pg


CHICAGO - Adding an experimental mRNA-based vaccine from Moderna Inc and Merck &
Co reduced the risk that the most deadly skin cancer would spread by 65 per cent
over treatment with an immunotherapy alone in a mid-stage trial, the companies
reported on Monday.

The results, presented at the American Society of Clinical Oncology meeting in
Chicago, follow earlier promising data from the trial showing the customised
mRNA vaccine given in combination with Merck’s Keytruda cut the risk of death or
recurrence of melanoma by 44 per cent compared with Keytruda alone.

The findings add to a growing body of evidence suggesting that mRNA technology,
which rose to prominence during the Covid-19 pandemic, can be used to assemble
personalised vaccines that train the immune system to attack the specific type
of cancer cells in a patient’s tumours.



Scientists have been chasing the dream of vaccines to treat cancer for decades
with few successes.

Experts say mRNA vaccines, which can be produced in as little as eight weeks,
paired with drugs that rev up the immune system may lead to a new generation of
cancer therapies.

The hope is for “a completely new treatment paradigm in cancer that will be
better tolerated and unique to individual patients’ tumours”, said Dr Jane
Healy, an executive overseeing in early cancer treatment development at Merck.




The Merck/Moderna collaboration is one of several combining powerful drugs that
unleash the immune system to target cancers with mRNA vaccine technology.
Pfizer’s Covid-19 vaccine partner BioNTech SE and Gritstone Bio Inc are taking
similar approaches using mRNA technology.



The vaccines all target neoantigens, new mutations that are only present on
tumours. Aiming at these unique proteins allows the immune system to kill cancer
cells while leaving healthy tissue unscathed.

The trick is determining which of many mutations is driving the cancer.

To accomplish this, tumours are removed, and their genetic makeup is mapped
using next-generation DNA sequencing.



Companies use artificial intelligence to predict which mutations will be the
most effective targets. These are used to build an individualised vaccine
targeting only mutations in the patient’s tumour.

During this process, patients typically receive an immunotherapy such as
Keytruda or Roche’s Tecentriq, which block a mechanism cancer uses to hide from
the immune system.

Long before Covid-19, companies had been eyeing messenger RNA (mRNA) technology,
which carries instructions for cells to make specific proteins, as a vehicle for
delivering a cancer vaccine.

Merck and Moderna have been collaborating since 2016. Researchers at Memorial
Sloan Kettering Cancer Centre (MSK) in New York began working with Germany’s
BioNTech in 2017.

At that time, there was already proof that immunotherapy could work in so-called
“hot” tumours, or highly mutated cancers, such as melanoma. There was little
hope it would work in “cold” cancers with few mutations, such as pancreatic
cancer, said MSK’s Dr Vinod Balachandran.

More On This Topic
Vaccine production in S’pore, Asean prepares region for future pandemics: CEO of
vaccine foundation
New Thermo Fisher Scientific drug facility for vaccine manufacture opens in
Singapore

With standard treatment, 90 per cent of pancreatic cancer patients die within
five years of diagnosis.

Dr Balachandran’s team studied the rare long-term survivors and found an immune
system component called T cells in these individuals were able to recognise
mutations derived from the cancer, raising the possibility of a targeted
vaccine.

In a small ongoing trial testing a made-to-order BioNTech vaccine plus Roche’s
Tecentriq, half of the 16 pancreatic cancer patients mounted an immune response,
and none showed signs of relapse after 18 months, according to data published
last month in Nature.

Gritstone Bio is taking a different tack, combining two types of customised
vaccines in hopes of treating patients with metastatic colon cancer, another
cancer that has been largely unresponsive to immunotherapy.

The approach first primes the immune system with an older technology called a
chimpanzee adenovirus vaccine that targets patients’ tumours.

That is followed by a personalised self-amplifying mRNA vaccine, which includes
an enzyme that makes extra copies of the antigens, reducing the required dose.

Gritstone is expecting data from a later-stage trial testing its dual vaccine
therapy in the first quarter of 2024.

“Based on everything we’ve shown and we’ve published, we’re really excited,”
said Gritstone CEO Andrew Allen.

Merck and Moderna are planning a larger Phase 3 trial in melanoma and are also
testing its combination in lung cancer.

“We see this as a starting point,” Dr Healy said. REUTERS

More On This Topic
Moderna says vaccines for cancer, heart disease could be ready by 2030
mRNA vaccines and heart issues: S’pore researchers identify possible link
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